Dual surface adsorbents whose outer surfaces are rendered hydrophilic and whose inner surfaces are modified by ligands have hitherto been used in the field of liquid chromatography and in the field of medical treatment. For example, when specified hydrophobic substances are removed from a sample liquid or blood, adsorbents whose outer surfaces are modified by hydrophilic ligands and whose inner surfaces are modified by ligands, are used in order to prevent a protein (for example, a blood coagulation factors) in the sample from adsorption on the outer surfaces of an adsorbents. Recently, applications of these dual surface adsorbents to removal of pathogenic blood constituents on bringing these adsorbents into contact with blood have been extensively investigated, where the resulting blood is then perfused into human body (a direct hemoperfusion method).
As the above-described adsorbents and production methods thereof, there have hitherto been known the method as described in JP-A-61-65159, the method as disclosed in JP-A-62-158113, and the method as disclosed in JP-A-3-218458.
The method as described in JP-A-61-65159 is a method in which porous silica particles having a glyceroylpropyl group introduced thereinto are used as a starting material, reacted with a carboxyl diimidazole compound, and subsequently bound to a hydrophobic oligopeptide (ligand), and the hydrophobic oligopeptide present on the outer surfaces of the silica particles is then decomposed by an enzyme. Accordingly, the thus produced particles exhibit hydrophilicity on the outer surfaces thereof, whereas they exhibit hydrophobicity in the inner portions thereof because the hydrophobic oligopeptide compound is held therein.
The method as disclosed in JP-A-62-158113 is a method in which silica particles having an octadecylsilyl group (hydrophobic group) introduced thereinto are used as a starting material and subjected to plasma processing, the hydrophobic group in an exposed area is eliminated, and the exposed area is converted to a silanol. When a hydrophilic organic group reactive with a silanol group is then introduced into the thus produced particles, the particles exhibit hydrophilicity on the surfaces thereof, whereas they exhibit hydrophobicity in the inner portions thereof.
The method as disclosed in JP-A-3-218458 is a method in which porous silica particles are brought into contact with a silicone polymer containing Si—H group, whereby the surfaces thereof are polymerized, and the resulting particles are reacted with a hydrocarbon compound containing vinyl group, or after converting the Si—H group into an Si—OH group, are reacted with an alkylsilane compound. The thus produced particles are then brought into contact with a Lewis acid under specific conditions to cleave the alkyl groups present on the outer surfaces thereof, and reacted with a hydrophilic silane compound. The resulting particles exhibit hydrophilicity on the surfaces thereof, whereas they exhibit hydrophobicity in the inner portions thereof.
As described above, the dual surface adsorbents are expected to have applications in various fields. But, according to the conventionally known methods, the production step is complicated and long. Further, in the case where, for example, an enzyme is used in the final surface processing, there is a problem that only those having a pore diameter such that the enzyme cannot enter the pores are produced.
In addition, in the case where the dual surface adsorbents are applied to the direct hemoperfusion method, a biocompatibility of the adsorbent to blood, i.e., a property that constitutional components of blood, such as platelets and proteins, are not adsorbed thereon, is important (see, for example, KOBUNSHI RONBUNSHU (“Japanese Journal of Polymer Science and Technology”), Vol. 39, No. 4, pp. 165-171 (1982); J. Biomater. Sci. Polymer Edn, Vol. 4, No. 4, pp. 381-400 (1993); and Trans. Am. Soc. Artif. Intern. Organs., Vol. 35, pp. 333-335 (1989)).